Finally a future perspective is also included.Bone is one of the most preferred sites of metastatic spread from different cancer types, including breast cancer. However, different breast cancer subtypes exhibit distinct metastatic behavior in terms of kinetics and anatomic sites of relapse. Despite advances in the diagnosis, the identification of patients at high-risk of bone recurrence is still an unmet clinical need. We conducted a retrospective analysis, by gene expression and immunohistochemical assays, on 90 surgically resected breast cancer samples collected from patients who experienced no evidence of distant metastasis, bone or visceral metastasis in order to identify a primary tumor-derived marker of bone recurrence. We identified trefoil factor-1 (pS2 or TFF1) as strictly correlated to bone metastasis from ER+ breast cancer. In silico analysis was carried out to confirm this observation, linking gene expression data with clinical characteristics available from public clinical datasets. Then, we investigated TFF1 function in ER+ breast cancer tumorigenesis and bone metastasis through xenograft in vivo models of MCF 7 breast cancer with gain and loss of function of TFF1. As a response to microenvironmental features in primary tumors, TFF1 expression could modulate ER+ breast cancer growth, leading to a less proliferative phenotype. Our results showed it may not play a role in late stages of bone metastasis, however further studies are warranted to understand whether it could contribute in the early-stages of the metastatic cascade. In conclusion, TFF1 upregulation in primary ER+ breast cancer could be useful to identify patients at high-risk of bone metastasis. This could help clinicians in the identification of patients who likely can develop bone metastasis and who could benefit from personalized treatments and follow-up strategies to prevent metastatic disease.Breast cancer frequently metastasizes to the skeleton causing significant morbidity. None of the therapeutic strategies used to manage breast cancer bone metastases are really curative. Here, we set-up a novel and advanced model by using fresh tissue from human vertebral bone metastasis from breast carcinoma patients able to retain the tumor microenvironment. The tissue model is based on an ex-vivo culture for up to 40 days and on a constant monitoring of tissue viability, gene expression profile (IL10, IL1b, MMP1, MMP7, PTH1R, PTH2R, TNF, ACP5, SPI1, VEGFA, CTSK, TGF-β) and histological and immunohistochemical analyses (CDH1/E-cadherin, CDH2/N-cadherin, KRT8/Cytokeratin 8, KRT18/Cytokeratin 18, Ki67, CASP3/Caspase 3, ESR1/Estrogen Receptor Alpha, CD68 and CD8). Results confirmed the development of a reliable, reproducible and cost-effective advanced model of breast cancer bone metastasis able to preserve and maintain long-term tissue viability, as well as molecular markers, tissue histomorphology, tissue micro-architecture and antigen expression. The study provides for the first time the feasibility and rationale for the use of a human-derived advanced alternative model for cancer research and testing of drugs and innovative strategies, taking into account patient individual characteristics and specific tumor subtypes so predicting patient specific responses.To investigate the effects of sequential therapy with monthly intravenous ibandronate on bone mineral density (BMD) and microstructure in patients with primary osteoporosis who received teriparatide treatment.
Sixty-six patients with primary osteoporosis who had undergone teriparatide treatment for more than 12months (mean 18.6months) received sequential therapy with 1mg/month intravenous ibandronate for 12months. The patients were evaluated using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound, bone turnover markers, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6 and 12months after beginning administration.
At 12months after beginning sequential therapy, the bone resorption marker, tartrate-resistant acid phosphatase-5b, decreased by 39.5%, with 82.3% of the patients exhibiting levels within the normal limit. https://www.selleckchem.com/products/brigimadlin.html DXA revealed that the BMD of the lumbar spine increased by 3.2%, with 79.0% of the patients exhibiting a response, and 40.3% experiencing an increase in BMD over 5%. HR-pQCT revealed that the cortical thickness of the distal tibia was increased by 2.6%. The cortical area increased by 2.5%, and the buckling ratio (an index of cortical instability) decreased by 2.5%. Most parameters of the trabecular bone showed no significant changes. These changes in the cortical bone were observed in both the distal radius and tibia and appeared beginning 6months after treatment initiation.
Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment.
Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment.Detraining after dedicated exercise programs might be a frequent situation in older people's exercise patterns. The aim of the present study was thus to determine the effects of 6months of detraining after 18months of high intensity resistance exercise (HIT-RT) on musculoskeletal outcomes in older men with sarcopenia.
Community-dwelling men aged 72years and older with osteosarcopenia (n=43) were randomly assigned to an 18-month HIT-RT (EG n=21) or a non-training control group (CG, n=22). After the intervention, participants of the EG stopped HIT-RT for 6months, but continued their habitual physical activity. Study outcomes were skeletal muscle mass index, bone mineral density (BMD) at the lumbar-spine and total-hip, maximum hip/leg-extensor strength, handgrip strength and gait velocity. We applied an intention-to-treat analysis with multiple imputation.
Changes in the HIT-RT were much more pronounced during the detraining period compared with the CG, although this effect was only significant for skeletal muscle mass index and hip-/leg-extensor strength (p=.